ICUs are settings of high antifungal consumption. Excessive antifungal use may cause individual and collective harm due to treatment-related adverse effects, drug–drug interactions and the selection of drug-resistant fungi, with increasing prevalence of fluconazole-resistant Candida (e.g. Candida glabrata and Candida krusei) and triazole-resistant Aspergillus (Aspergillus fumigatus) reported. Optimizing antifungal use to attain the best clinical outcomes for patients, while preventing resistance emergence and minimizing drug toxicity, are key aims of antifungal stewardship (AFS) programmes. Challenges to AFS in the ICU include critical illness severity potentially driving overuse and hindering de-escalation, and organ dysfunction or drug–drug interactions restricting prescribing options from the limited antifungal classes available. There are few data on prescribing practices in ICUs to guide antifungal stewardship implementation in this setting.
An antifungal therapy (AFT) service evaluation (15 May–19 November 2019) across ICUs at three London hospitals, evaluating consumption, prescribing rationale, post-prescription review, de-escalation and final invasive fungal infection (IFI) diagnostic classification.
Overall, 6.4% of ICU admissions (305/4781) received AFT, accounting for 11.41 days of therapy/100 occupied bed days (DOT/100 OBD). The dominant prescribing mode was empirical (41% of consumption), followed by targeted (22%), prophylaxis (18%), pre-emptive (12%) and non-invasive (7%). Antifungal prescribing for suspected or confirmed IFI accounted for 75% of consumption in critical care and was predominantly empirical , with a further 18% used for prophylaxis (2.11 DOT/100 OBD) and 7% for non-invasive infection (0.75 DOT/100 OBD) (Table 1 and Figure 1).
Echinocandins were the most commonly prescribed drug class (4.59 DOT/100 OBD). In total, 217 patients received AFT for suspected or confirmed IFI; 12%, 10% and 23% were classified as possible, probable or proven IFI, respectively. Hence, in 55%, IFI was unlikely. Proven IFI (n = 50) was mostly invasive candidiasis (92%), of which 48% had been initiated on AFT empirically before yeast identification. Where on-site (1 3)-β-D-glucan (BDG) testing was available (1 day turnaround), in those with suspected but unproven invasive candidiasis, median (IQR) AFT duration was 10 (7–15) days with a positive BDG (≥80 pg/mL) versus 8 (5–9) days with a negative BDG (<80 pg/mL). Post-prescription review occurred in 79% of prescribing episodes (median time to review 1 [0–3] day). Where suspected IFI was not confirmed, 38% episodes were stopped and 4% de-escalated within 5 days.
Better, evidence-based risk prescribing techniques including fast diagnostics to guide AFT start and stop decisions are needed to strike a better balance between treating IFI patients as soon as possible and preventing unnecessary antifungal prescriptions in the ICU.
Source: C Logan, C Hemsley, A Fife, J Edgeworth, A Mazzella, P Wade, A Goodman, P Hopkins, D Wyncoll, J Ball, T Planche, S Schelenz, T Bicanic, A multisite evaluation of antifungal use in critical care: implications for antifungal stewardship, JAC-Antimicrobial Resistance, Volume 4, Issue 3, June 2022, dlac055, https://doi.org/10.1093/jacamr/dlac055.